The objective of this project continues to be the use of NMR (and other spectroscopic methods) to learn about the mobility and relative orientations of groups in polypeptides and proteins, and thereby determine the conformations of these molecules in solution. In some cases, the results of these experiments will be combined with those from conformational energy calculations to reduce the ambiguities present in both the spectroscopic and computational techniques. The primary aim is to solve structural problems related to biological function. Various two-dimensional NMR techniques are being applied to natural and synthetic polypeptides and proteins in solution. Each system is selected to answer a specific conformational question, e.g. the mechanism of folding of ribonuclease, and the structures of onc gene products and growth factors (related to cancer).